Impact of experimental design on PET radiomics in predicting somatic mutation status

Purpose: PET-based radiomic features have demonstrated great promises in predicting genetic data. However, various experimental parameters can influence the feature extraction pipeline, and hence, Here, we investigated how experimental settings affect the performance of radiomic features in predicting somatic mutation status in non-small cell lung cancer (NSCLC) patients. Methods: 348 NSCLC patients with somatic mutation testing and diagnostic PET images were included in our analysis. Radiomic feature extractions were analyzed for varying voxel sizes, filters and bin widths. 66 radiomic features were evaluated. The performance of features in predicting mutations status was assessed using the area under the receiver-operating-characteristic curve (AUC). The influence of experimental parameters on feature predictability was quantified as the relative difference between the minimum and maximum AUC (delta). Results: The large majority of features (n = 56, 85%) were significantly predictive for EGFR mutation status (AUC >= 0.61). 29 radiomic features significantly predicted EGFR mutations and were robust to experimental settings with delta(Overall) < 5%. The overall influence (delta(Overall)) of the voxel size, filter and bin width for all features ranged from 5% to 15%, respectively. For all features, none of the experimental designs was predictive of KRAS + from KRAS-(AUC <= 0.56). Conclusion: The predictability of 29 radiomic features was robust to the choice of experimental settings; however, these settings need to be carefully chosen for all other features. The combined effect of the investigated processing methods could be substantial and must be considered. Optimized settings that will maximize the predictive performance of individual radiomic features should be investigated in the future.